Adult Leukemia Research Center Program Project The overall goal of this program project is to improve allogeneic hematopoietic cell transplantation (HCT) as treatment for hematological malignancies. Specifically, we propose laboratory and clinical studies to increase the safety of transplantation, to enhance the anti-tumor effects of transplantation, to broaden the availability of transplantation, and to improve our ability to apply transplantation at the appropriate time in the course of disease. Six individual projects are proposed: 1. Nonmyeloablative Hematopoietic Cell Allotransplants 2. Immunogenetics of Graft-Versus-Host Disease 3. Prevention and Treatment of Graft-Versus-Host Disease 4. Resistance and Relapse of Chronic Myeloid Leukemia 5. Specific Adoptive Immunotherapy of Leukemia 6. Targeting Alloreactivity for Leukemia Eradication In addition, core support is requested in biostatistics, pathology, microbiology and virology, gastroenterology, pulmonary medicine and nephrology, cell processing, long-term follow-up, and administration. Our ability to successfully carry out the proposed work is greatly benefited by: (1) the existence of a large group of investigators all focused on the general topic of HCT; (2) strong preclinical research programs at our Center in support of this topic; and (3) the accrual of 450-500 transplant patients onto research protocols each year. Relevance to Public Health: This Program Project has direct relevance to the more than 18,000 patients who undergo allogeneic HCT for treatment of hematopoietic malignancies each year. The work proposed promises to make transplantation safer, more effective, increasingly available and more appropriately applied. Further, lessons learned from our planned studies will apply to issues of transplant tolerance, the molecular basis of malignant disease progression, and especially the immunotherapy of cancer.